Dihydroimidazo[5,1-a]sg(b)-carboline derivatives, method for preparing same and use thereof as medicine

ABSTRACT

The invention concerns dihydroimi-dazo[5,1-a]-β-carboline compounds of general formula (1), wherein in particular, R 1 , R 2 , R 2 , R a , R 6  and K 7 , identical or different, independently of one another, represent a hydrogen, halogen atom, an alkyl, hydroxy, alkoxy, trihalogenoalkyl, alkylamino, dialkylamino, aryl, arylalkyl, carboxy, alkylcarbonyloxy, acyl, aryloxy or arylalkoxy group; R 3  represents a hydrogen atom, an alkyl or arylalkoxy group; and their isomers as well as their addition salts to a pharmaceutically acceptable acid. The inventive compounds arm for use as medicine, in particular as hypnotic.

The present invention concerns novel derivatives ofdihydroimidazo[5,1-a]-β-carboline with general formula (I):

in which:R₁, R₂, R₃ and R₄, which may be identical or different, independentlyrepresent a hydrogen atom, a halogen atom, a linear or branched (C₁-C₆)alkyl group, a hydroxyl group, a linear or branched (C₁-C₆) alkoxygroup, a linear or branched trihalogeno (C₁-C₆)alkyl group, a linear orbranched trihalogeno (C₁-C₆)alkoxy group, a nitro group, a cyano group,an amino group, a linear or branched (C₁-C₆)alkylamino group, a linearor branched di(C₁-C₆)alkylamino group, an aryl group, a linear orbranched aryl(C₁-C₆)alkyl group, a carboxyl group, a linear or branched(C₁-C₆)alkylcarbonyloxy group, a linear or branched (C₁-C₆) acyl group,an aryloxy group or a linear or branched aryl(C₁-C₆)alkoxy group;R₅ represents a hydrogen atom, a linear or branched (C₁-C₆) alkyl groupor a linear or branched aryl(C₁-C₆)alkyl group;R₆ and R₇, which may be identical or different, independently representa hydrogen atom, a halogen atom, a linear or branched (C₁-C₆) alkylgroup, a hydroxyl group, a linear or branched (C₁-C₆) alkoxy group, alinear or branched trihalogeno(C₁-C₆)alkyl group, a linear or branchedtrihalogeno(C₁-C₆)alkoxy group, a cyano group, an amino group, a linearor branched (C₁-C₆)alkylamino group, a linear or brancheddi(C₁-C₆)alkylamino group, an aryl group, a linear or branchedaryl(C₁-C₆)alkyl group, a carboxyl group, a linear or branched(C₁-C₆)alkylcarbonyloxy group, a linear or branched (C₁-C₆) acyl group,an aryloxy group or a linear or branched aryl(C₁-C₆)alkoxy group; theirisomers and their addition salts with a pharmaceutically acceptableacid.

In the present description, the term “aryl” means a phenyl, naphthyl,tetrahydronaphthyl, dihydronaphthyl, indenyl or indanyl group, each ofsaid groups optionally being substituted, in an identical or differentmanner, with one or more halogen atoms, hydroxyl, cyano, nitro, linearor branched (C₁-C₆) alkyl, linear or branched (C₁-C₆) alkoxy, amino,linear or branched (C₁-C₆) alkylamino, linear or branched di(C₁-C₆)alkylamino, aryloxy, linear or branched aryl(C₁-C₆)alkoxy, linearor branched (C₁-C₆)trihalogenoalkyl, linear or branched (C₁-C₆) acyl,linear or branched (C₁-C₆)alkoxycarbonyl, linear or branched (C₁-C₆)alkylaminocarbonyl or oxo groups.

In an advantageous variation, preferred compounds of the invention arethose in which:

R₁, R₃ and R₄ represent a hydrogen atom;

R₆ and R₇ independently represent a hydrogen atom, a linear or branched(C₁-C₆) alkyl group or an aryl group; and

R₅ represents a hydrogen atom, or a linear or branched (C₁-C₆) alkylgroup.

Preferred substituents R₂ in accordance with the invention are ahydrogen atom, a halogen atom (fluorine, chlorine or bromine), a linearor branched (C₁-C₆) alkyl group, a hydroxyl group and a linear orbranched (C₁-C₆) alkoxy group.

Preferred compounds of the invention are:

-   3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-methoxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-methoxy-5,6-dihydroimidazo[5,1-a]-β-carboline;-   8-methoxy-3-methyl-1-phenyl-5,6-dihydroimidazo[5,1-a]-β-carboline;-   1-ethyl-8-methoxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline;-   8-methoxy-3-isopropyl-5,6-dihydroimidazo[5,1-a]-β-carboline;-   8-methoxy-3-propyl-5,6-dihydroimidazo[5,1-a]-β-carboline;-   8-methoxy-11-methyl-3-propyl-5,6-dihydroimidazo[5,1-a]-β-carboline    methane sulfonate;-   8-methoxy-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline    methane sulfonate;-   8-hydroxy-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline    methane sulfonate;-   8-hydroxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate;-   8-chloro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-methoxy-3-phenyl-5,6-dihydroimidazo[5,1-a]-β-carboline;-   11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-chloro-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-chloro-3-methyl-11-ethyl-5,6-dihydroimidazo[5,1-a]-β-carboline    methane sulfonate;-   3,8-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline-   methane sulfonate;-   3,8,11-trimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   11-ethyl-3,8-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-fluoro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-bromo-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-fluoro-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane    sulfonate;-   8-fluoro-11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline    methane sulfonate;-   8-bromo-11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline    methane sulfonate.

The invention also pertains to a method for preparing compounds withformula (I), characterized in that the starting product used is acompound with formula (II):

in which R₁, R₂, R₃, R₄ and R₅ have the meanings given in formula (I),said compound with formula (II) being reacted under peptide couplingsynthesis conditions with a compound with formula (III):

in which R₆ and R₇ are as defined in formula (I), to produce a compoundwith formula (IV):

in which R₁, R₂, R₃, R₄, R₅, R₆ and R₇ are as defined above, thecompound with formula (IV) being treated in the presence of phosphorousoxychloride in a solvent such as toluene to produce compounds withformula (I):

in which R₁, R₂, R₃, R₄, R₅, R₆ and R₇ are as defined above, thecompounds with general formula (I) together forming the compounds of theinvention which are transformed if appropriate into their addition saltswith a pharmaceutically acceptable acid.

The compounds with formula (II) and (III) are either commerciallyavailable compounds, or are obtained using known methods of organicsynthesis.

The present invention also pertains to pharmaceutical compositionscomprising, as the active principle, at least one compound with formula(I), its addition salts with a pharmaceutically acceptable acid, usedalone or in combination with one or more nontoxic and pharmaceuticallyacceptable excipients or inert vehicles.

More particular pharmaceutical compositions of the invention that can becited are those which are suitable for oral, parenteral (intravenous,intramuscular or subcutaneous), per- or transcutaneous, nasal, rectal,perlingual, ocular or respiratory administration, and in particular assimple or sugar-coated tablets, sublingual tablets, sachets, gelules,lozenges, suppositories, creams, pomades, skin gels, injectable ordrinkable preparations, aerosols, or eye or nose drops.

The following examples illustrate the invention without in any waylimiting its scope.

Dihydroimidazo[5,1-a]-β-carboline derivatives have been described in theprior art as intermediates in the synthesis of the following:

R₁═R₂=R₃═R₄=R₅═R₆═H and R₇═CH₃: Kanaoke Y; Sato E; Yonemitsu O;Tetrahedron, 1968, 24, 2591-2594.

R₁═R₂=R₃═R₄=R₅═R₆═H and R₇=Ph: Elliott, J. Org. Chem., 1962, 3302-3305.

Clearly, those derivatives are only described as intermediates in asynthesis and have no known therapeutic activity. They only fall withinthe scope of the present invention in the context of a drug, inparticular as a hypnotic.

The starting products and/or the reagents used are products that areknown or prepared using known methods.

The structures of the compounds described in the examples and the stagesof the synthesis were determined using the usual spectrophotometrictechniques (infrared, NMR, mass spectroscopy).

In order to illustrate the subject matter of the present invention,there follow some examples of derivatives with general formula I inwhich R₁═R₃ R₄═H:

TABLE I EXAMPLE R₂ R₅ R₆ R₇ Example 1 H CH₃ H CH₃ Example 2 CH₃O H H CH₃Example 3 CH₃O H H H Example 4 CH₃O H Ph CH₃ Example 5 CH₃O H CH₃CH₂ CH₃Example 6 CH₃O H H CH(CH₃)₂ Example 7 CH₃O H H (CH₂)₂CH₃ Example 8 CH₃OCH₃ H (CH₂)₂CH₃ Example 9 CH₃O CH₃ H CH₃ Example 10 OH CH₃ H CH₃ Example11 OH H H CH₃ Example 12 H H H CH₃ Example 13 Cl H H CH₃ Example 14 CH₃OH H Ph Example 15 H CH₃CH₂ H CH₃ Example 16 Cl CH₃ H CH₃ Example 17 ClCH₃CH₂ H CH₃ Example 18 CH₃ H H CH₃ Example 19 CH₃ CH₃ H CH₃ Example 20CH₃ CH₃CH₂ H CH₃ Example 21 F H H CH₃ Example 22 Br H H CH₃ Example 23 FCH₃ H CH₃ Example 24 F CH₃CH₂ H CH₃ Example 25 Br CH₃CH₂ H CH₃

EXAMPLE 1 3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methanesulfonate Operating Mode A:2-acetylamino-N-[2-(1H-indol-3-yl)-ethyl]acetamide

Diphenylphosphorylazide (5.8 ml, 27.5 ml) and triethylamine (3.85 ml,27.5 ml) were added in succession to a mixture of tryptamine (4.32 g, 27mmol) and N-acetylglycine (3.3 g, 28 mmol) in DMF (100 ml) cooled to 0°C. The mixture was stirred under nitrogen at ambient temperature for 12h, then the solvent was eliminated under reduced pressure. The residueobtained was flash chromatographed on silica gel to produce the expectedproduct (m=5.5 g, 21 mmol), giving a yield of 78%.

Operating Mode B:2-acetylamino-N-[2-(1-methyl-1H-indol-3-yl)-ethyl]acetamide

NaH at 60% in oil (0.35 g, 8.75 mmol) and an alkyl halide (CH₃I, 0.55ml, 8.83 mmol) were added to the amide (2 g, 8.23 mmol) obtained inoperating mode A in DMF (20 ml). It was stirred for 12 hours at ambienttemperature before eliminating the solvent under reduced pressure. Theexpected product was obtained after flash chromatography on silica gel(1.02 g, 3.96 mmol), giving a yield of 48%.

Operating Mode C: 3,11-dimethyl-5,6-dihydroimidazo-[5,1-a]-β-carbolinemethane sulfonate

The amide (1.02 g, 3.96 mmol) from operating mode B was heated to refluxin toluene (V=50 ml). POCl₃ (10 ml) in toluene (15 ml) was added over 30min. The reaction mixture was concentrated under reduced pressure andthe residue was taken up in ethanol (5 ml), then NaOH was added (20%, 50ml). It was stirred for 30 min, then the solid formed was recovered byfiltering. The product was purified by flash chromatography on silicagel; the expected product was obtained (280 mg, 1.26 mmol; Yield=32%).

To obtain 3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methanesulfonate dissolved in ethanol, methane sulfonic acid (1 equivalent) wasadded and the corresponding mesylate was obtained by precipitation.

¹H NMR (300 MHz, CDCl₃): 2.72 (s, 3H); 2.78 (s, 3H); 3.23 (t, J=6.9 Hz,2H), 3.71 (s, 3H); 4.22 (t, J=6.9 Hz, 2H); 7.11 (m, 2H); 7.24 (s, 2H),7.48 (m, 2H).

MS (m/z) 237 (100); 221; 195; 181.

EXAMPLE 2 8-methoxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-methoxytryptamine andN-acetylglycine as substrate during operating mode A; the amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHz, CDCl₃): 2.40 (s, 3H); 2.80 (s, 3H); 3.00 (t, J=6.6 Hz,2H), 3.80 (s, 3H); 3.96 (t, J=6.6 Hz, 2H); 6.78 (m, 2H); 7.20 (d, J=8.8Hz, 1H), 7.50 (s, 1H).

EXAMPLE 3 8-methoxy-5,6-dihydroimidazo[5,1-a]-β-carboline

The procedure of Example 1 was followed using 5-methoxytryptamine andN-formylglycine as substrate during operating mode A; the amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 3.09 (t, J=6.9 Hz, 2H); 3.82 (s,3H); 4.2 (t, J=6.9 Hz, 2H); 6.79 (dd, J=2.4 and 8.8 Hz, 1H); 6.91 (d,J=2.4 Hz, 1H); 7.10 (s, 1H); 7.23 (d, J=8.8 Hz, 1H); 7.50 (s, 1H).

MS (m/z) 239 (100); 196; 168; 140.

EXAMPLE 48-methoxy-3-methyl-1-phenyl-5,6-dihydro-imidazo[5,1-a]-β-carboline

The procedure of Example 1 was followed using 5-methoxytryptamine andN-acetyl-2-phenylglycine as substrate during operating mode A; the amideobtained was used directly in the cyclization reaction of operating modeC.

¹H NMR (300 MHz, CDCl₃): 2.5 (s, 2H); 3.15 (t, J=6.9 Hz, 2H); 3.85 (s,3H), 4.08 (t, J=6.9 Hz, 2H), 6.8 (dd, J=2.4 and 8.8 Hz, 1H); 6.94 (d,J=2.4 Hz, 1H); 7.15 (d, J=8.8 Hz, 1H); 7.36 (m, 1H); 7.46 (m, 2H); 7.74(m, 2H); 8.30 (s, 1H).

MS (m/z) 329 (100); 286; 165; 143.

EXAMPLE 51-ethyl-8-methoxy-3-methyl-5,6-dihydro-imidazo[5,1-a]-β-carboline

The procedure of Example 1 was followed using 5-methoxytryptamine andN-acetyl-2-ethylglycine as substrate during operating mode A; the amideobtained was used directly in the cyclization reaction of operating modeC.

¹H NMR (300 MHz, CDCl₃): 1.30 (t, 7 Hz, 3H); 2.43 (s, 3H); 2.80 (q, 7Hz, 2H); 3.11 (t, J=7 Hz, 2H); 3.88 (s, 3H), 4.06 (t, J=7 Hz, 2H); 6.83(dd, J=2.4 and 8.7 Hz, 1H); 6.97 (d, J=2.4 Hz, 1H); 7.27 (d, J=8.7 Hz,1H); 8.71 (broad s, 1H).

MS (m/z) 281 (100); 266; 250; 233.

EXAMPLE 6 8-methoxy-3-isopropyl-5,6-dihydroimidazo-[5,1-a]-β-carboline

The procedure of Example 1 was followed using 5-methoxytryptamine andN-isobutyrylglycine as substrate during operating mode A; the amideobtained was used directly in the cyclization reaction of operating modeC.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 1.33 (d, J=6.8 Hz, 6H); 3.04 (m,4H); 3.86 (s, 3H); 4.04 (t, J=6.8 Hz, 2H); 6.79 (d, J=8.76 Hz, 1H), 6.95(s, 1H); 6.98 (s, 1H); 7.22 (d, J=8.76 Hz, 1H); 10.30 (s, 1H).

MS (m/z) 281 (100); 266; 196; 133

EXAMPLE 7 8-methoxy-3-propyl-5,6-dihydroimidazo[5,1-a]-β-carboline

The procedure of Example 1 was followed using 5-methoxytryptamine andN-butyrylglycine as substrate during operating mode A; the amideobtained was used directly in the cyclization reaction of operating modeC.

¹H NMR (300 MHz, CDCl₃): 1.00 (t, 7.5 Hz, 3H); 1.76 (m, 2H); 2.70 (t,7.5 Hz, 2H); 3.08 (t, J=7.5 Hz, 2H); 3.87 (s, 3H); 3.97 (t, J=7.5 Hz,2H); 6.81 (dd, J=2.7 and 8.7 Hz, 1H), 6.88 (d, J=2.7 Hz, 1H); 7.08 (s,1H); 7.28 (d, J=8.7 Hz, 1H); 10.38 (broad s, 1H).

MS (m/z) 281 M+; 269; 252 (100); 209.

EXAMPLE 88-methoxy-11-methyl-3-propyl-5,6-dihydro-imidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-methoxytryptamine andN-butyrylglycine as substrate during operating mode A.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 1.06 (t, 7.5 Hz, 3H); 1.83 (m, 2H);2.75 (t, 7.5 Hz, 2H); 3.08 (t, J=6.8 Hz, 2H); 3.8 (s, 3H); 3.88 (s, 3H),4.06 (t, J=6.8 Hz, 2H); 6.86 (dd, J=2.4 and 8.7 Hz, 1H), 6.96 (d, J=2.4Hz, 1H); 7.15 (s, 1H); 7.18 (d, J=8.7 Hz, 1H).

MS (m/z) 295 (100); 266; 223; 133.

EXAMPLE 9 8-methoxy-3,11-dimethyl-5,6-dihydroimidazo-[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-methoxytryptamine andN-acetylglycine as substrate during operating mode A.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 2.44 (s, 3H); 3.05 (t, J=6.9 Hz,2H); 3.77 (s, 3H); 3.85 (s, 3H), 3.99 (t, J=6.9 Hz, 2H); 6.86 (dd, J=2.4and 8.7 Hz, 1H); 6.93 (d, J=2.4 Hz, 1H); 7.15 (d, J=8.7 Hz, 1H).

MS (m/z) 267 (100); 251; 235; 224.

EXAMPLE 108-hydroxy-3,11-dimethyl-5,6-dihydroimidazo-[5,1-a]-β-carboline methanesulfonate

8-methoxy-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline (Example9, m=300 mg, 1 mmol) was dissolved in anhydrous dichloromethane at −78°C. BBr₃ (V=8 ml) was added and the temperature was allowed to return toambient temperature over 12 hours with stirring and in a nitrogenatmosphere. A solution of (2M) NaHCO₃ (15 ml) was added. Afterdecanting, the product precipitated from the dichloromethane and theexpected product was recovered (m=150 mg, 0.6 mmol, Yield=50%).

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 2.45 (s, 3H); 3.05 (t, J=6.7 Hz,2H); 3.84 (s, 3H), 4.06 (t, J=6.7 Hz, 2H); 6.80 (d, J=8.7 Hz, 1H), 6.91(s, 1H); 7.15 (d, J=8.7 Hz, 1H).

MS (m/z) 253 (100); 224; 211; 126.

EXAMPLE 11 8-hydroxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carbolinemethane sulfonate

8-methoxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline (Example 2,m=350 mg, 1.4 mmol) was dissolved in anhydrous dichloromethane at −78°C. BBr₃ (V=8 ml) was added and the temperature was allowed to return toambient temperature over 12 hours with stirring and in a nitrogenatmosphere. A solution of (2M) NaHCO₃ (15 ml) was added. Afterdecanting, the product precipitated from the dichloromethane and theexpected product was recovered (m=200 mg, 0.83 mmol, Yield=59%).

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 2.67 (s, 3H); 3.19 (t, J=7.2 Hz,2H); 4.21 (t, J=7.2 Hz, 2H); 6.78 (dd, J=2.4 and 8.7 Hz, 1H), 6.88 (d,J=2.4 Hz, 1H); 7.23 (d, J=8.7 Hz, 1H).

EXAMPLE 12 3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methanesulfonate

The procedure of Example 1 was followed using tryptamine andN-acetylglycine as substrate during operating mode A. The amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHz, CDCl₃): 2.53 (s, 3H); 3.08 (t, J=6.8 Hz, 2H); 3.99 (t,6.8 Hz, 2H); 7.04 (m, 2H); 7.16 (m, 2H); 7.36 (s, 1H); 7.44 (d, 1H).

MS (m/z) 223 (100); 208; 181; 154.

EXAMPLE 13 8-chloro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-chlorotryptamine andN-acetylglycine as substrate during operating mode A. The amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 2.72 (s, 3H); 2.81 (s, 3H); 3.16(t, J=6.9 Hz, 2H); 4.13 (t, J=6.9 Hz, 2H); 7.12 (dd, J=2 and 8.7 Hz,1H); 7.31 (d, J=8.7 Hz, 1H); 7.44 (d, J=2 Hz, 1H); 7.52 (s, 1H).

MS (m/z) 257 (100); 242; 221; 215.

EXAMPLE 14 8-methoxy-3-phenyl-5,6-dihydroimidazo[5,1-a])-β-carboline

The procedure of Example 1 was followed using 5-methoxytryptamine andhippuric acid as substrate during operating mode A. The amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHz, CD₃COCD₃): 2.87 (s, 3H); 3.16 (t, J=6.8 Hz, 2H); 3.82(s, 3H), 4.45 (t, J=6.8 Hz, 2H); 6.77 (dd, J=2.4 and 9.6 Hz, 1H); 7.05(d, J=2.4 Hz, 1H); 7.30 (s, 1H); 7.31 (d, J=9.6 Hz, 1H); 7.52 (m, 3H);7.75 (m, 2H); 8.02 (s, 1H).

MS (m/z) 315 (100); 272; 211; 168.

EXAMPLE 15 11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using tryptamine andN-acetylglycine as substrate during operating mode A. The alkylationagent for operating mode B was ethyl bromide.

¹H NMR (300 MHz, CD₃OD): 1.33 (t, 7.1 Hz, 3H); 2.76 (s, 3H); 2.78 (s,3H); 3.25 (t, J=6.9 Hz, 2H); 4.24 (m, 4H); 7.12 (t, 1H); 7.3 (m, 2H);7.49 (d+1s, 2H).

EXAMPLE 16 8-chloro-3,11-dimethyl-5,6-dihydroimidazo-[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-chlorotryptamine andN-acetylglycine as substrate during operating mode A.

¹H NMR (300 MHz, CDCl₃): 2.60 (s, 3H); 2.70 (s, 3H); 3.16 (t, J=6.8 Hz,2H); 4.20 (t, J=6.8 Hz, 2H); 7.12 (d, J=8.8 Hz, 1H); 7.25 (d, J=8.8 Hz,1H); 7.50 (s, 1H); 7.6 (s, 1H).

MS (m/z): 271 (100); 235; 193; 167.

EXAMPLE 178-chloro-3-methyl-11-ethyl-5,6-dihydro-imidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-chlorotryptamine andN-acetylglycine as substrate during operating mode A. The alkylationagent for operating mode B was ethyl bromide.

¹H NMR (300 MHz, CDCl₃): 1.39 (t, J=4.8 Hz, 3H); 2.70 (s, 3H); 2.85 (s,3H); 3.2 (t, J=7 Hz, 2H); 4.3 (m, 4H); 7.2 (dd, J=2.4 and 8.8 Hz, 1H);7.35 (d, J=8.8 Hz, 1H); 7.53 (d, J=2.4 Hz, 1H); 7.6 (s, 1H).

MS (m/z): 285 (100); 270; 249; 180.

EXAMPLE 18 3,8-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methanesulfonate

The procedure of Example 1 was followed using 5-methyltryptamine andN-acetylglycine as substrate during operating mode A. The amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 2.43 (s, 3H); 2.61 (s, 3H); 2.85(s, 3H); 3.14 (t, J=7 Hz, 2H); 4.08 (t, J=7 Hz, 2H); 7.05 (d, 8.6 Hz,1H); 7.28 (s, 1H); 7.32 (d, J=8.6 Hz, 1H); 7.51 (s, 1H)

MS (m/z) 237 (50); 129; 73; 55 (100).

EXAMPLE 19 3,8,11-trimethyl-5,6-dihydroimidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-methyltryptamine andN-acetylglycine as substrate during operating mode A.

¹H NMR (CDCl₃:CD₃OD/90:10): 2.40 (s, 3H); 2.70 (s, 3H); 2.75 (s, 3H);3.2 (t, J=6.9 Hz, 2H); 3.75 (s, 3H); 4.18 (t, J=6.9 Hz, 2H); 7.07 (d,J=8.5 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H); 7.27 (s, 1H); 7.50 (s, 1H).

MS (m/z) 251 (100); 235; 203.

EXAMPLE 20 11-ethyl-3,8-dimethyl-5,6-dihydroimidazo-[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-methyltryptamine andN-acetylglycine as substrate during operating mode A. The alkylationagent for operating mode B was ethyl bromide.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 1.32 (t, J=7.2 Hz, 3H); 2.40 (s,3H); 2.72 (s, 3H); 2.78 (s, 3H); 3.21 (t, J=6.9 Hz, 2H); 4.19 (m, 4H);7.08 (d, J=8.4 Hz, 1H); 7.20 (d, J=8.4 Hz, 1H); 7.29 (s, 1H); 7.45 (s,1H).

MS (m/z): 265 (100); 250; 236; 223.

EXAMPLE 21 8-fluoro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-fluorotryptamine andN-acetylglycine as substrate during operating mode A. The amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHZ, CDCl₃:CD₃OD/90:10): 2.60 (s, 3H); 2.75 (s, 3H); 3.09(t, J=7 Hz, 2H); 4.10 (t, J=7 Hz, 2H); 6.87 (dt, J=2.4 and 9 Hz, 1H),7.02 (dd, J=2.4 and 9 Hz, 1H); 7.26 (dd, J=3 and 9 Hz, 1H); 7.50 (s,1H).

MS (m/z) 241 (100); 226; 199; 172.

EXAMPLE 22 8-bromo-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-bromotryptamine andN-acetylglycine as substrate during operating mode A. The amide obtainedwas used directly in the cyclization reaction of operating mode C.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 2.68 (s, 3H); 2.86 (s, 3H); 3.19(t, J=7.2 Hz, 2H); 4.20 (t, J=7.2 Hz, 2H); 7.28 (m, 2H); 7.34 (s, 1H);7.58 (s, 1H); 7.61 (s, 1H).

MS (m/z) 301/302 (100); 286; 259; 234.

EXAMPLE 23 8-fluoro-3,11-dimethyl-5,6-dihydroimidazo-[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-fluorotryptamine andN-acetylglycine as substrate during operating mode A.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 2.78 (s, 3H); 2.83 (s, 3H); 3.25(t, J=6.9 Hz, 2H); 4.31 (t, J=6.9 Hz, 2H); 7.07 (dt, J=2.4 and 9 Hz,1H); 7.22 (dd, J=2.4 and 9 Hz, 1H); 7.32 (dd, J=3 and 9 Hz, 1H); 7.66(s, 1H).

MS (m/z) 255 (100); 213; 185; 128.

EXAMPLE 248-fluoro-11-ethyl-3-methyl-5,6-dihydro-imidazo[5,1-a]-β-carbolinemethane sulfonate

The procedure of Example 1 was followed using 5-fluorotryptamine andN-acetylglycine as substrate during operating mode A. The alkylationagent for operating mode B was ethyl bromide.

¹H NMR (CDCl₃:CD₃OD/90:10): 1.32 (t, J=7.2 Hz, 3H); 2.70 (s, 3H); 2.80(s, 3H); 3.16 (t, J=6.9 Hz, 2H); 4.2 (m, 4H); 6.97 (dt, J=2.4 and 9 Hz,1H), 7.13 (dd, J=2.4 and 9 Hz, 1H); 7.23 (dd, J=4 and 9 Hz, 1H); 7.65(s, 1H).

MS (m/z): 269 (100); 254; 227; 199.

EXAMPLE 258-bromo-11-ethyl-3-methyl-5,6-dihydro-imidazo[5,1-a]-β-carboline methanesulfonate

The procedure of Example 1 was followed using 5-bromotryptamine andN-acetylglycine as substrate during operating mode A. The alkylationagent for operating mode B was ethyl bromide.

¹H NMR (300 MHz, CDCl₃:CD₃OD/90:10): 1.32 (t, J=7 Hz, 3H); 2.70 (s, 3H);2.75 (s, 3H); 3.18 (t, J=7 Hz, 2H); 3.59 (s, 3H); 4.20 (m, 4H); 7.19 (d,J=8.7 Hz, 1H); 7.30 (dd, J=1.8 and 8.7 Hz, 1H); 7.53 (s, 1H); 7.63 (d,J=1.8 Hz, 1H).

MS (m/z): 329/330 (100); 316; 300; 273.

The dihydroimidazo[5,1-a]-β-carboline derivatives of the invention, inparticular those in the form of the methyl sulfonate, (soluble), weretested in chicks, and certain compounds that were active in the chickwere administered in single doses to six Beagle dogs of both sexes for apolysomnographic study of at least 4 hours duration.

Experimental Protocol for the Chick

JA 657 chicks from Couvoir Gauguet, 44 Le Pin, were accustomed for atleast 6 days to an alternating program of light and darkness with 12hours of daylight and 12 hours of darkness at a regulated temperature of25±2° C. They were fed ad libitum and were placed under test compoundsin a vivarium in groups of 3 individuals with a mean weight of 100±10 gon the day of the test. At that age in this species, there is noeffective meningeal (hemato-encephalic) barrier. The test products wereinjected in 3 doses (1, 3 and 10 mg/kg) intramuscularly (IM) in solutionor in an aqueous suspension (1 drop of Tween 80 per ml), each to twobatches of 3 chicks which were observed over 90 minutes. For each testseries (18 vivaria), there was at least one batch of negative controlchicks receiving the same volume (0.2 ml IM) of water for injectablepreparations.

During the 90 minute observation period, the chicks were stronglystimulated every 15 minutes by presenting a full feeding trough, andeach 5 minute period was given a grade from among the following 5states, corresponding to the state of alertness over that period:

Mobile, sitting alert, drowsy, asleep, sleep-like state. The parametersstudied were the time to torpor (TA) passed between injection and thefirst stage of sleep, the duration of the first sleep (TS) and the totalsedation time over the period (Tsed), expressed in minutes and as a % ofthe period (Sed).

To compare the results of tests carried out at different dates, theextension of the duration of the first sleep TS compared with the testcontrols was recorded.

Results

In the untested chick of the same age, the wake-sleep cycle lasts 20 to30 minutes during the day. Thus, it appears that from a dose of 1 mg, atleast 11 compounds (out of 20) induced a very substantial reduction inlocomotive activity, as shown by a first sleep period TS of more than 20minutes.

At higher doses, the number of test products in this category changed to18/20 and 20/20 for 3 and 10 mg/kg.

There is a clear positive dose-effect relationship for the majority ofthe test compounds, with a reduction in the onset of torpor when thedose is increased.

Over 90 minutes, the difference in the sedation time compared with thatobserved using a placebo was more than 52 minutes for 2 compounds from adose of 1 mg/kg, for 4 compounds at 3 mg/kg and for 12 compounds at 10mg/kg. TABLE II (Dose: 1 mg/kg) TS (mins) TA TS Tsed Sed PlaceboCOMPOUNDS Mins Mins Mins % diff'ce Example 1 7 56.5 64.5 71.7 56 Example2* 16 3 25 27.8 3 Example 3* 10 40 66.51 73.9 36 Example 4* 16.5 3853.01 58.9 34 Example 5* 20.5 33 52.47 58.3 29 Example 6* 11 56.5 65.9773.3 52.5 Example 7* 16.5 16 46 41.4 16 Example 8 16 21.5 38 42.2 21Example 9 22 3 24.5 27.2 2.8 Example 10 15 5 38 42.2 4.7 Example 11 40 026.5 29.4 −0.3 Example 12 10 39.5 46.5 51.7 39 Example 13 16.5 33.5 5257.8 33 Example 14* 7 35.5 62.865 63.5 32 Example 15 12.5 12 21.5 23.921 Example 16 11.5 15 37 41 14.7 Example 17 12 12 37 41.1 11.7 Example18 5 32.5 62.5 69.4 24 Example 19 4 17.5 44.5 49.4 11 Example 20 2 65.572 80 57*in the form of the free base

TABLE III (Dose: 3 mg/kg) TS (mins) TA TS Tsed Sed Placebo COMPOUNDSMins Mins Mins % diff'ce Example 1 4.5 78.5 78.5 87.2 78 Example 2* 8.541 62.5 69.4 41 Example 3* 7 66.5 71.0 78.9 62.5 Example 4* 14 22.5 65.572.8 18.5 Example 5* 14.5 53 69.0 76.7 49 Example 6* 12.5 72.5 72.5 80.668.5 Example 7* 16.5 27 45.5 41 27 Example 8 8.5 33 54 60 32.7 Example 917.5 13.5 26.5 29.4 13 Example 10 30 1 11 12.2 0.7 Example 11 15 7 34.538.3 6.7 Example 12 3.5 42 57.5 63.9 41.7 Example 13 9.5 73 73 81.1 73Example 14* 15 34 61.2 68 31.5 Example 15 7 29.5 40.5 45 29 Example 1613.5 20.5 30.5 33.9 20 Example 17 7.5 23.5 30 33.3 23 Example 18 4.530.5 57.5 63.9 22.5 Example 19 3.5 46.5 56.5 62.8 38.5 Example 20 1.551.5 71.5 79.4 43.5*in the form of the free base

TABLE IV (Dose: 10 mg/kg) TS (mins) TA TS Tsed Sed Placebo COMPOUNDSMins Mins Mins % diff'ce Example 1 1 86 87 96.7 85.7 Example 2* 7 83 8392.2 83 Example 3* 6.5 77.5 78.0 86.7 73.5 Example 4* 8.5 81.5 81.5 90.676.5 Example 5* 13.5 40.5 56.5 62.8 36.5 Example 6* 12.5 72.5 74.0 82.268.5 Example 7* 12.5 38.5 53.5 48.2 38.5 Example 8 5.5 41 68.5 76.1 40.7Example 9 16.5 15.5 38.5 42.8 15 Example 10 11.5 12.5 27 30 12 Example11 6 9.5 18.5 20.6 9 Example 12 1 89 89 98.9 88.7 Example 13 4 86 8695.6 85.7 Example 14* 7 28 63 70 25.5 Example 15 1 70 72 80 69.7 Example16 7.5 31 52.5 58.3 52 Example 17 5 43.5 60.5 67.2 43 Example 18 7.5 7681.5 90.6 68 Example 19 3.5 60 67.5 75.0 52 Example 20 1.5 87.5 87.597.2 81.5*in the form of the free baseExperimental Protocol for the Dog

Polysomnographic tests were carried out for each of the three productsfrom the series, on 6 dogs of both sexes, adults from the certifiedbreeding kennels at HARLAN, 03 Gannat, using stainless steel electrodessurgically implanted for the duration of the test in contact with thefrontal bones through the sinus, facing the motor regions of theencephalus. The Nishino et al method adapted by Tafani, Valin et al hasbeen described elsewhere. It comprised recording two traces for eyemovements, one trace for muscular movements (concentric electrode in thenape muscles) and two electroencephalographic (EEG) traces. The digitalEEG trace was recorded using a Nicollet Schwarzer polygraph or the like(DELTAMED Coherence 2 and 3, MEI Galileo NT) for 4 hours afteradministering a 00 gelule containing 0, 16 or 48 mg of the test product(i.e. a mean of 0,1 and 3 mg/kg of live weight).

Each dog was monitored for 4 hours twice a day over two days, morningand afternoon, after one week's acclimatization to the monitoring cage,a 1 m 2, 80 cm high stainless steel cage of the SHOR-LINE type. For eachdog, monitoring always commenced at the same time. A meal wasdistributed 30 minutes before starting monitoring.

The polysomnographic traces could differentiate between at least 4stages for each consecutive 30 second period: awake, somnolence, slowsleep and paradoxal sleep. The latency of the appearance of each of thefirst nonalert episodes and the duration of each of the stages per 2hour period were recorded for each dog. Comparing the means allowed theeffect of the test products on the sleep microstructure to be studied.

Results:

Latencies: Tables V to VII: TABLE V Slow wave Paradoxal Somnolence sleep(SWS) (REM) sleep Dose minutes minutes minutes Placebo 1 + 2 70 ± 6  98± 20 137 ± 4  Example 2 (1 mg)   40 ± 14.7   44 ± 16.3 114 ± 53  Example2 (3 mg)  37 ± 6.7  45 ± 5.4   63 ± 21.1

TABLE VI Slow wave Paradoxal Somnolence sleep (SWS) (REM) sleep Doseminutes minutes minutes Placebo 1 69 ± 58 79 ± 60 100 ± 62  Example 13(1 mg)   25 ± 11.6   32 ± 11.5   63 ± 28.2 Placebo 2   40 ± 13.1   50 ±23.8   62 ± 22.4 Example 13 (3 mg)  27 ± 9.1 35 ± 11   56 ± 19.5

TABLE VII Slow wave Paradoxal Somnolence sleep (SWS) (REM) sleep Doseminutes minutes minutes Placebo 1 71 ± 39.8 102 ± 71.8 125 ± 66.9Example 1 (1 mg) 47 ± 19.1  52 ± 24.8 101 ± 80.3 Placebo 2 44 ± 20.4  61± 27.6  87 ± 30.2 Example 1 (3 mg) 21 ± 7.1  27 ± 8.0  50 ± 22.2

The three test products show a clear reduction in the latency of thefirst somnolence, which is clearer in the 3 mg/kg dose for the productof Example 1. The latency of the first slow sleep episode (characterizedby spikes on the EEG traces) was halved compared with the overall testproducts.

The three compounds induce a positive hypnagogic effect.

Time passed at each alert stage: Tables VIII to X. TABLE VIII AlertnessSomnolence SWS REM Dose minutes minutes minutes minutes Placebo 1 + 2147 ± 35.5 25 ± 10.3 59 ± 21.9 8.5 ± 5.4 Example 2 136 ± 40.3 31 ± 4.6 59 ± 20.5 13.5 ± 10.6 (1 mg) Example 2 123 ± 30.5 36 ± 15.4 60 ± 26.9 20 ± 9.5 (3 mg)

TABLE IX Alertness Somnolence SWS REM Dose minutes minutes minutesminutes Placebo 1 156 ± 38.5  26 ± 11.3 39 ± 23.9 19 ± 11.4 Example 135± 44.3 24 ± 2.6 57 ± 26.5 21 ± 13.6 13 (1 mg) Placebo 2 140 ± 27.9 32 ±7.3 47 ± 19.9 21 ± 10   Example 13 122 ± 36.5 31 ± 7   61 ± 24.9 26 ±13.5 (3 mg)

TABLE X Alertness Somnolence SWS REM Dose minutes minutes minutesminutes Placebo 1 154 ± 35.2 30 ± 16.0 45 ± 19.4 11 ± 8.5  Example 1 139± 69.1 27 ± 10.4 51 ± 42.3 23 ± 19.1 (1 mg) Placebo 2 134 ± 36.5 35 ±21.4 50 ± 34.8 20 ± 10.8 Example 1 106 ± 34.7 40 ± 10.9 65 ± 30.2 29 ±13.7 (3 mg)

Over the four hours of monitoring, a tendency for the alertness periodto reduce was observed, in particular for the dose of 3 mg/kg for thethree compounds. This reduction in alertness was accomplishedessentially by an increase in the slow sleep and paradoxal sleep stages.

The observed effects were manifested more clearly during the first twohours, particularly for the dose of 1 mg/kg, which could correspond tothe product elimination kinetics.

The three compounds exhibit hypnotic properties.

In contrast to known compounds, there was no modification in thepercentage somnolence nor in that of the paradoxal sleep in the nonalertperiod.

The imidazopyridoindole derivatives of the invention all exhibited apharmacological activity on the central nervous system of at least twoanimal species. They reduced alertness, accelerating the onset of sleep(positive hypnagogic effect). In the chick and the dog, there was areduction in alert activity. In this latter species, there was nomodification in sleep ultrastructure. Thus, they are useful as drugs, inparticular as hypnotics.

1. Compounds of dihydroimidazo[5,1-a]-β-carboline with general formula (I):

in which: R₁, R₂, R₃ and R₄, which may be identical or different, independently represent a hydrogen atom, a halogen atom, a linear or branched (C₁-C₆) alkyl group, a hydroxyl group, a linear or branched (C₁-C₆) alkoxy group, a linear or branched trihalogeno (C₁-C₆) alkyl group, a linear or branched trihalogeno (C₁-C₆) alkoxy group, a nitro group, a cyano group, an amino group, a linear or branched (C₁-C₆) alkylamino group, a linear or branched di (C₁-C₆) alkylamino group, an aryl group, a linear or branched aryl (C₁-C₆) alkyl group, a carboxyl group, a linear or branched (C₁-C₆) alkylcarbonyloxy group, a linear or branched (C₁-C₆) acyl group, an aryloxy group or a linear or branched aryl (C₁-C₆) alkoxy group; R₅ represents a hydrogen atom, a linear or branched (C₁-C₆) alkyl group or a linear or branched aryl (C₁-C₆) alkyl group; and R₆ and R₇, which may be identical or different, independently represent a hydrogen atom, a halogen atom, a linear or branched (C₁-C₆) alkyl group, a hydroxyl group, a linear or branched (C₁-C₆) alkoxy group, a linear or branched trihalogeno (C₁-C₆) alkyl group, a linear or branched trihalogeno (C₁-C₆) alkoxy group, a cyano group, an amino group, a linear or branched (C₁-C₆) alkylamino group, a linear or branched di (C₁-C₆) alkylamino group, an aryl group, a linear or branched aryl (C₁-C₆) alkyl group, a carboxyl group, a linear or branched (C₁-C₆) alkylcarbonyloxy group, a linear or branched (C₁-C₆) acyl group, an aryloxy group, or a linear or branched aryl (C₁-C₆) alkoxy group; with the exception, however, of compounds with general formula I in which R₁ to R₆ represent a hydrogen atom and R₇ represents a CH₃ group or a phenyl group; their isomers and their addition salts with a pharmaceutically acceptable acid.
 2. The compounds as claimed in claim 1, wherein: R₁, R₃ and R₄ represent a hydrogen atom; R₆ and R₇ independently represent hydrogen, a linear or branched (C₁-C₆) alkyl group or an aryl group, in particular a phenyl group; and R₅ represents a hydrogen atom, or a linear or branched (C₁-C₆) alkyl group.
 3. The compounds as claimed in claim 1, wherein: R₂ represents a hydrogen atom, a halogen atom, a linear or branched (C₁-C₆) alkyl group, a hydroxyl group or a linear or branched (C₁-C₆) alkoxy group.
 4. The compounds as claimed in claim 1, which are selected from the following compounds: 3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-5,6-dihydroimidazo[5,1-a]-β-carboline; 8-methoxy-3-methyl-1-phenyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 1-ethyl-8-methoxy-3-methyl-5,6-dihydroimidazo[5, 1-a]-β-carboline; 8-methoxy-3-isopropyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 8-methoxy-3-propyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 8-methoxy-11-methyl-3-propyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-hydroxy-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-hydroxy-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-chloro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-methoxy-3-phenyl-5,6-dihydroimidazo[5,1-a]-β-carboline; 11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-chloro-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-chloro-3-methyl-11-ethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 3,8-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 3,8,11-trimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 11-ethyl-3,8-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-fluoro-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-bromo-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-fluoro-3,11-dimethyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-fluoro-11-ethyl-3-methyl-5,6-dihydroimidazo[5,1-a]-β-carboline methane sulfonate; 8-bromo-11-ethyl-3-methyl-5,6-dihydroimidazo[5, 1-a]-β-carboline methane sulfonate.
 5. A method for preparing compounds with formula (I) as claimed in claim 1, wherein a compound with formula (II):

in which R₁, R₂, R₃, R₄ and R₅ have the meanings given in formula (I), is reacted under peptide coupling synthesis conditions with a compound with formula (III):

in which R₆ and R₇ are as defined in formula (I), to produce a compound with formula (IV):

in which R₁, R₂, R₃, R₄, R₅, R₆ and R₇ have the meanings defined above, the compound with formula (IV) being treated in the presence of phosphorous oxychloride in a solvent such as toluene to produce compounds with formula (I)

in which R₁, R₂, R₃, R₄, R₅, R₆ and R₇ are as defined above, the compounds with general formula (I) being transformed if appropriate into their addition salts with a pharmaceutically acceptable acid.
 6. Pharmaceutical compositions comprising, as the active principle, at least one compound with formula (I) or one of its addition salts with a pharmaceutically acceptable acid as claimed in claim 1, in combination with one or more nontoxic and pharmaceutically acceptable excipients or inert vehicles.
 7. A method for treatment comprising administering an effective amount of a compound as claimed in claim 1 to a patient in need of such treatment.
 8. A method for treating a patient with a hypnotic drug comprising administering an effective amount of a compound as claimed in claim 1 to a patient in need of such treatment. 